Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.

Polymicrogyria in infants with symptomatic congenital cytomegalovirus at birth is associated with epilepsy: A retrospective, descriptive cohort study.

Aim: To identify neonatal magnetic resonance imaging (MRI) features that predict the likelihood of children with congenital cytomegalovirus (cCMV) developing epilepsy, together with clinical features and a validated MRI scoring system.

Method: This was a retrospective descriptive cohort study of infants with cCMV referred to a paediatric infectious disease centre between April 2012 and March 2022, and followed up for at least 2 years. MRI was performed before 4 months of age and assessed by two paediatric neuroradiologists.

Three-dimensional analysis of facial morphology in nine-year-old children with different unilateral orofacial clefts compared to normative data.

Aim: To compare three-dimensional (3D) facial morphology of various unilateral cleft subphenotypes at 9-years of age to normative data using a general face template and automatic landmarking. The secondary objective is to compare facial morphology of 9-year-old children with unilateral fusion to differentiation defects.

Methods: 3D facial stereophotogrammetric images of 9-year-old unilateral cleft patients were imported into 3DMedX® for processing.

Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers.

Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction.

Ethical considerations on surrogacy†.

Surrogacy is the assisted reproductive technology (ART) practice in which a person becomes pregnant, carries, and delivers a child on behalf of another couple/person, who are the intended parent(s). Surrogacy is an especially complex practice as the interests of the intended parents, the gestational carrier, and the future child may differ. This paper considers ethical questions related to different forms of surrogacy.

Sleep Behaviour in Sickle Cell Disease: A Systematic Review and Meta-Analysis.

There is a high prevalence of sleep behaviour disorders, as well as sleep disordered breathing (SDB), in individuals living with sickle cell disease (SCD). SDB has been systematically reviewed; therefore, this systematic review and meta-analysis focused on sleep behaviour. The comprehensive literature search, following PRISMA reporting guidelines, included all languages, conference proceedings and published theses from inception through February 2022.

International benchmarking of stage at diagnosis for six childhood solid tumours (the BENCHISTA project): a population-based, retrospective cohort study.

Background: International variation in childhood cancer survival might be explained by differences in stage at diagnosis, among other factors. As part of the BENCHISTA project, we aimed to assess geographical variation in tumour stage at diagnosis through the application, by population-based cancer registries working with clinicians, of the international consensus Toronto Childhood Cancer Stage Guidelines.

Methods: This population-based, retrospective cohort study involved 67 cancer registries from 23 European countries, Australia, Brazil, Japan, and Canada.

Admission to acute medical wards for mental health concerns among children and young people in England from 2012 to 2022: a cohort study.

Background: There are challenges in providing high quality care for children and young people who are admitted to acute medical wards for mental health concerns. Although there is concern that these admissions are increasing, national data describing these patterns are scarce. We aimed to describe trends in these admissions in England over a 10-year period, and to identify factors associated with repeat admission and length of stay.

Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families.

The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments is vital for various cellular functions, particularly within the nervous system, where microtubules play a key role in intracellular transport, cell morphology, and synaptic plasticity. Tubulin-specific chaperones, including tubulin folding cofactors (TBCA, TBCB, TBCC, TBCD, TBCE), assist in the proper formation of α/β-tubulin heterodimers, essential for microtubule stability. Pathogenic variants in these chaperone-encoding genes, especially TBCD, have been linked to Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT, OMIM #604,649), a severe neurodevelopmental disorder.

Spectral Analysis of Light-Adapted Electroretinograms in Neurodevelopmental Disorders: Classification with Machine Learning.

Electroretinograms (ERGs) show differences between typically developing populations and those with a diagnosis of autism spectrum disorder (ASD) or attention deficit/hyperactivity disorder (ADHD). In a series of ERGs collected in ASD ( = 77), ADHD ( = 43), ASD + ADHD ( = 21), and control ( = 137) groups, this analysis explores the use of machine learning and feature selection techniques to improve the classification between these clinically defined groups. Standard time domain and signal analysis features were evaluated in different machine learning models.

Mediation of the effect of prenatal maternal smoking on time to natural menopause in daughters by birthweight-for-gestational-age z-score and breastfeeding duration: analysis of two UK birth cohorts born in 1958 and 1970.

Background: Prenatal maternal smoking, lower birthweight, and shorter breastfeeding duration have all been associated with an earlier age at menopause in daughters. We estimated the extent to which birthweight-for-gestational-age z-score and breastfeeding duration mediate the effect of prenatal maternal smoking on time to natural menopause in daughters.

Methods: Using pooled data from two prospective birth cohort studies - the 1970 British Cohort Study (n = 3,878) followed-up to age 46 years and the 1958 National Child Development Study (n = 4,822) followed-up to age 50 years - we perform mediation analysis with inverse odds weighting implemented in Cox proportional-hazards models.

Predictors of specialist care referrals (SCR) following emergency department review or hospital admission in adults with previous acute COVID-19: a prospective UK cohort study.

Background: Long-COVID research to date focuses on outcomes in non-hospitalised vs. hospitalised survivors. However Emergency Department attendees (post-ED) presenting with acute COVID-19 may experience less supported recovery compared to people admitted and discharged from hospital (post-hospitalised group, PH).

Patients' reasons for declining a primary care trial online therapy: a mixed methods study.

Background: Integrating therapist-led sessions and Cognitive Behavioural Therapy (CBT) materials within one online platform may be effective for people with depression. A trial evaluating this mode of delivering CBT is being conducted. To maximize future trial recruitment and understand patients' views of health interventions, it is important to explore reasons for declining to participate.

Survey of legislative frameworks and national recommendations governing paediatric maintenance haemodialysis in Europe.

Background: The application of international recommendations for paediatric maintenance haemodialysis (HD) could be strengthened by national laws or written recommendations. Our aim was therefore to describe the national rules governing paediatric maintenance HD in European countries.

Methods: A national representative, approved by the president of each paediatric nephrology society, was contacted in all 42 European countries to complete two online questionnaires.

Young people's experiences of informal kinship care in Luwero, Uganda.

There is strong evidence that outside parental care, informal kinship care is the most practiced, sustainable and affordable form of childcare in SSA (sub-Saharan Africa). As a longstanding cultural tradition, informal kinship care embraces childcare as the responsibility of all extended family members, and often the wider community. However, over the past decades, informal kinship care has become gradually strained by political, economic and social conditions, such as: legacies of colonialism, increasing levels of poverty and inequality, instability, or infectious diseases.

Adapting a consensus process for survivors of domestic abuse and child maltreatment: a brief report about adopting a trauma-informed approach in multistakeholder workshops.

Purpose: Among health researchers, there is a growing appreciation of the importance of the involvement of service users and members of the public. This recognition has not only resulted in involvement guidelines and improved research ethics but also an increasing use of consensus processes with service users and members of the public to determine research priorities and questions and to agree outcomes to be measured in intervention studies. There is, however, limited advice about how to safely involve survivors of violence and abuse in consensus-based studies.

Spinal presentations in children with type 1 spinal muscular atrophy on nusinersen treatment across the SMA-REACH UK network: a retrospective national observational study.

Background: Prior to the introduction of disease-modifying treatments (DMTs), children with type 1 spinal muscular atrophy (SMA) typically did not survive beyond the age of 2 years; management was mainly palliative. Novel therapies have made this a treatable condition, resulting in increased life expectancy and more time spent upright. Survival and improved function mean spinal asymmetry is a new complication with limited data on its prevalence and severity and no current guidelines on management and treatment.

Measuring the visual environment of children and young people at risk of myopia: a scoping review.

Purpose: Myopia (short-sightedness) is an emerging WHO priority eye disease. Rise in prevalence and severity are driven by changes in lifestyle and environment of children and young people (CYP), including less time spent in bright daylight and more time spent on near-vision activities. We aimed to systematically map the literature describing direct, objective measurements of the visual environment of CYP.

Six at Sixty. 'Have you tested for 22q?'.

In 1997, the published our paper on the spectrum of clinical features associated with interstitial chromosome 22q11 deletions. This copy number variation is associated with an extraordinary range of clinical features, which led initially to its association with several diagnostic labels. Since 1997 work on clinical and basic science aspects of the syndrome and the genes reduced to hemizygosity have provided a wealth of information pertaining to both best practice care and underlying biology.

Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.

 Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players.

Reducing the risk of visual disability for children with juvenile idiopathic arthritis uveitis through disease surveillance: past and future challenges.

Childhood blindness significantly impacts development, education, employment, and mental health, creating burden for families and society. Between 8% and 30% of children with Juvenile Idiopathic Arthritis (JIA) develop a potentially blinding chronic inflammatory eye disease, uveitis (JIAU). Alongside the use of disease-modifying agents and anti-TNF immunomodulators, JIAU surveillance has helped to reduce the risk of JIAU related blindness.